Abstract
BackgroundPatients with atypical values of HCG and/or PAPP-A are at higher risk of chromosomal abnormality and vascular complications of pregnancy. The performance of cfDNA in this particular population has not yet been evaluated.ObjectivesThe primary objective was to evaluate the usefulness and reliability of cfDNA in screening for trisomy 21, 18 and 13 for patients with HCG < 0.25 multiple of median (MoM), HCG > 5.0 MoM and/or PAPP-A < 0.25 MoM, PAPP-A > 2.5 MoM. The secondary objective was to evaluate the contribution of cfDNA assay for the prediction of pregnancy’s vascular complications.MethodBetween June 2016 and July 2017, we analysed a women cohort from all over France who had at least one first trimester serum biomarker outside of normal range, in a retrospective, observational and multicentre study. Patients were included if they had a single pregnancy, normal first trimester ultrasound examination, whatever the result of the combined first trimester screening test was. The cfDNA was analysed by massive parallel sequencing technique. The accuracy of cfDNA assay was evaluated by calculation of sensitivity and specificity, and multivariate regression analysis was used to search for predictive factors for pregnancy’s vascular complications.ResultsAmong the 498 patients who underwent a cfDNA assay in this context, twenty-one (4.2%) were excluded because of loss to follow-up. Out of 477, test failure occurred for four patients initially, reduced to two patients (0.4%) after redrawn. CfDNA was positive for Trisomy 21 (n = 19), Trisomy 18 (n = 6) and Trisomy 13 (n = 1) and negative in 449. The sensitivity of cfDNA assay for trisomy 21 screening was 100% (19/19) (IC 95% 82.4–100) and specificity 100% (458/458) (IC 95% 99.2–100). Among the 447 patients included for prediction of vascular complications, there were four cases of pregnancy induced hypertension and 10 cases of preeclampsia, for which no predictive factor was identified. Intra Uterine growth restriction under 5th percentile (n = 44, 9.8%) was significantly associated with a low fetal fraction (OR = 0.87, IC 95% 0.79–0.96, p = 0.006).ConclusioncfDNA assay is an effective and reliable tool for women with atypical profile of first trimester serum biomarkers.
Highlights
Cell free fetal DNA test has widely proved its performance in prenatal screening for trisomy 21, 18 and 13, in both high risk and general population [1, 2].Carrara et al J Transl Med (2019) 17:398In the past few years, its use in clinical practice has been increasing constantly, due to its excellent sensitivity and specificity, added to its non-invasive character
Among the 447 patients included for prediction of vascular complications, there were four cases of pregnancy induced hypertension and 10 cases of preeclampsia, for which no predictive factor was iden‐ tified
Performance of Cell free fetal DNA (cfDNA) assaying for trisomy 21 in a cohort of patients with atypical first trimester screening serum results seem to be similar to that reported in the general population
Summary
Cell free fetal DNA (cfDNA) test has widely proved its performance in prenatal screening for trisomy 21, 18 and 13, in both high risk and general population [1, 2].Carrara et al J Transl Med (2019) 17:398In the past few years, its use in clinical practice has been increasing constantly, due to its excellent sensitivity and specificity, added to its non-invasive character. The software applies a truncation model, and uses the most extreme value useable but not the real one This could lead to an underestimation of the calculated risk, and it has been described that these patients with abnormally high or low HCG or PAPP-A values have a higher risk of abnormal karyotypes [3]. We have chosen to study women with first trimester screening test’s atypical profile (high or low HCG and PAPP-A rate), whatever the result of the combined test In this population, it has been described a higher risk of vascular complications during pregnancy, such as preeclampsia (PE) and intra uterine growth restriction (IUGR) [4,5,6,7]. The performance of cfDNA in this particular population has not yet been evaluated
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